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Imaging flow cytometry (IFC) provides single‐cell imaging data at a high acquisition rate. It is increasingly used in image‐based profiling experiments consisting of hundreds of thousands of multi‐channel images of cells. Currently available software solutions for processing microscopy data can provide good results in downstream analysis, but are limited in efficiency and scalability, and often ill‐adapted to IFC data. In this work, we propose Scalable Cytometry Image Processing (SCIP), a Python software that efficiently processes images from IFC and standard microscopy datasets. We also propose a file format for efficiently storing IFC data. We showcase our contributions on two large‐scale microscopy and one IFC datasets, all of which are publicly available. Our results show that SCIP can extract the same kind of information as other tools, in a much shorter time and in a more scalable manner. [ABSTRACT FROM AUTHOR]

Background: Young adults represent a third of the United Kingdom prison population and are at risk of poor health outcomes, including drug and alcohol misuse, self-harm and suicide. Court diversion interventions aim to reduce the negative consequences of criminal sanctions and address the root causes of offending. However, evidence of their effectiveness has not yet been established. The Gateway programme, issued as a conditional caution, aimed to improve the life chances of young adults committing low-level offences. Participants agreed not to reoffend during the 16-week caution and, following a needs assessment, received individual support from a Gateway navigator and attended two workshops encouraging analysis of own behaviour and its consequences. Objective: To evaluate the effectiveness and cost-effectiveness of Gateway in relation to health and well-being of participants compared to usual process (court summons or a different conditional caution). Design, setting and participants: Pragmatic, multisite, parallel-group, superiority randomised controlled trial with two 6-month internal pilots and a target sample size of 334. Randomisation between Gateway and usual process was on a 1 : 1 basis. Four Hampshire Constabulary sites recruited 18- to 24-year-old residents of Hampshire and Isle of Wight who were questioned for an eligible low-level offence. Semistructured interviews were also held with a sample of Gateway programme participants, staff and police study recruiters. Main outcome measures: Primary outcome was the Warwick-Edinburgh Mental Wellbeing Scale score at 12 months. Secondary outcomes included health status, alcohol and drug use, recidivism and resource use. Results: Recruitment commenced in October 2019 and the trial stopped in April 2021. A total of 191 participants were recruited, with 109 randomised to Gateway and 82 to usual process. Due to an initial overestimation of potentially eligible young people and low retention rates, recruitment targets were adjusted, and a range of mitigating measures introduced. Although recruitment broadly met study progression criteria [35/50 (70%) Pilot 1: 64/74 (86%) Pilot 2], retention was low throughout (overall: data collected at week 4 was 50%: at week 16 it was 50%: 1-year 37%). Low retention was multifactorial, with one of the main barriers being difficulties contacting participants. It was therefore not possible to complete the randomised controlled trial or the health economics analyses. Qualitative interviews held with 58 individuals yielded rare insights into the benefits and limitations of this type of intervention, as well as barriers and facilitators in relation to recruitment in this setting. Limitations: Despite close collaboration with the police to address recruitment and consent issues, expansion of the inclusion criteria and recruitment area and introducing other measures, the researchers were unable to collect sufficient data within an acceptable timeframe. Conclusions: The Gateway study was a unique endeavour to gather evidence for a potentially life-changing intervention for an underserved population. The experience gained indicates that randomised controlled trials of interventions, with a health-related outcome, are possible in this setting but point towards the need for conservative recruitment and retention estimates in this target population. Other study designs should be considered. The qualitative evaluation provided a range of valuable lessons for those seeking to design similar interventions or conduct research in similar settings. Study registration: This study is registered as ISRCTN11888938. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: 16/122/20) and is published in full in Public Health Research; Vol. 12, No. 7. See the NIHR Funding and Awards website for further award information. Plain language summary: Young adults who commit low-level offences often have many health and social needs, making them vulnerable to physical and mental health problems. The Gateway programme was a conditional caution developed to address the underlying causes of low-level offending in young people aged 18–24 years and hence improve their life chances. In Gateway, a mentor assessed the young person's needs and supported them, signposting to healthcare, housing or other services as required. The young people also participated in two workshops, analysing the causes and consequences of their behaviour. To find out if Gateway improved health and reoffending rates, a group of those who received a Gateway conditional caution were compared with a group of those receiving a court summons or a different conditional caution. Of the 191 participants recruited to the study, 109 were randomised to Gateway and 82 to the usual process. However, the researchers had significant difficulties getting hold of the study participants on the phone and they were unable to collect enough information from them to be able to say whether Gateway worked. The researchers introduced various changes to overcome this, but in the end had to stop the study early. As part of the study, the researchers interviewed 28 Gateway programme participants, 17 Gateway project staff and 13 police officers and staff who had been recruiting into the study. From the interviews the study discovered the perceived benefits of Gateway, how programmes like this could be improved and which factors helped or got in the way of doing research in the police setting. The Gateway study aimed to provide evidence for a potentially life-changing intervention for vulnerable young adults. Although it proved impossible to complete the study, the lessons learnt from running it should help colleagues design similar programmes or plan research studies with similar populations or in similar settings. Scientific summary: Background: Young adults represent a third of the United Kingdom (UK) prison population and are at risk of poor health outcomes including drug and alcohol misuse, self-harm and suicide. Those aged between 18 and 24, who have been questioned as suspects in relation to a low-level offence, may need to attend court and, if convicted, face penalties such as imprisonment. However, other means aimed at preventing young adults from reoffending exist. Court diversion interventions aim to reduce the negative consequences of some types of criminal sanctions and focus resources on addressing the root causes of offending. Although diversions are widely used in the UK, evidence of their effectiveness in terms of health outcomes has not yet been established using robust research methods. Hampshire Constabulary (HC), working with local charities, developed the Gateway programme, an out-of-court disposal aimed at improving the life chances of young adults. Objectives: The aim of this study was to evaluate the effectiveness and cost-effectiveness of the Gateway programme issued as a conditional caution (intervention) compared to usual process (court appearance or a different conditional caution). The study objectives were to: Examine the effectiveness of the Gateway intervention on: (1) health and well-being including alcohol and substance use, (2) access to and use of health and social services and (3) quality of life, among young adult offenders. Explore the views and experiences of victims. Assess the quantity and quality of the Gateway intervention as delivered in the study and the generalisability of the findings. Identify and measure relevant consequences, both cost and benefits, of the Gateway intervention compared with usual process. Examine the effectiveness of the Gateway intervention on recidivism. Methods: Design: The study undertook a pragmatic, superiority RCT with two 6-month internal pilot phases and qualitative evaluation: an economic evaluation was planned. Participants were randomised using a 1 : 1 allocation ratio to either the Gateway conditional caution (intervention) or disposal as usual to a court summons or a different conditional caution to Gateway (usual process). The qualitative evaluation aimed to capture the experiences and perceptions of the impact of the intervention on participants, the police, victims and those delivering the intervention. Participants, setting and recruitment: Eligible participants were those aged 18–24 who had committed low-level offences and resided within Hampshire and Isle of Wight (IoW) area. Participants were recruited by Police investigators during processing for an offence. Potential participants were offered a chance by the police to receive the Gateway caution, and those interested were invited to take part in the study. Police officers obtained Stage 1 consent and carried out an eligibility check, after which those eligible were automatically randomised to receive either a Gateway caution or follow the usual process, such as court appearance or a different conditional caution. Qualitative interviews were undertaken with trial participants, police officers and those delivering the intervention. Sample size: There is no widely accepted and established minimal clinically significant difference for the primary outcome, Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS). A change of three or more points is likely to be important to individuals. There is also variation in the standard deviation (SD) of the WEMWBS with estimates ranging from 6 to 10.8 with the pooled estimate of 10 across all studies. Assuming 90% power, 5% 2-sided statistical significance, mean difference of 4 points on WEMWBS and a SD of 10, 266 participants were required. Conservatively, assuming a 20% attrition rate, the study aimed to recruit and randomise 334 participants. Interventions: The Gateway programme, issued as a conditional caution, required participants to undertake a health and social care needs assessment, attend workshops encouraging analysis of their behaviour and its consequences, and agree not to reoffend during the 16-week caution. Usual process was disposal to a court summons or an alternative conditional caution. Outcomes: The primary outcome measure was the WEMWBS. Participants self-reported WEMWBS at 4-weeks, 16-weeks and 1-year post-randomisation. Secondary outcomes were health status [Short Form 12 questionnaire (SF-12)]; alcohol [Alcohol Use Disorders Identification Test (AUDIT)] and drug [Adolescent Drug Involvement Scale (ADIS)] use; type and frequency of reoffending (police data); and health and social care resource use (self-reported). Statistical methods: The original plan, pre-specified in version 1.0 of the SAP , was to carry out a repeated measures, mixed-effects linear regression model with the WEMWBS score at 4-weeks, 16-weeks and 1-year post-randomisation as the dependent variable, adjusting for treatment group, time, group by time interaction, total number of records management system incidents and police national computer convictions 1-year prerandomisation, age at randomisation, Index of Multiple Deprivation quintile at randomisation, pandemic time period and standard of usual process available as fixed effects. Recruiting site was to be adjusted for as a random effect. However, due to the study closing early because of issues with retaining participants, a descriptive analysis was undertaken with no formal hypothesis testing. All outcomes were summarised descriptively by a randomised treatment group. Qualitative evaluation: A qualitative evaluation was conducted to assess the implementation of the Gateway programme, including any related issues and observed benefits to the clients. Focusing on implementation, mechanisms and context, the research questions were: How is Gateway being implemented? What are the barriers to the implementation and effects of the Gateway programme? What are the mechanisms through which the intervention brings about change? How do different delivery methods (face-to-face/virtual/telephone) influence the above questions? We conducted qualitative interviews and focus groups with a range of stakeholders across three time periods during the implementation of the Gateway programme. Economic evaluation: A formal health economic analysis was not feasible. Health economic data are summarised descriptively with the trial data. Results: Randomised controlled trial: We recruited 191 participants; 109 were randomised to Gateway and 82 to usual process. Although recruitment rates were within acceptable limits, the number of participants providing data [94 (32%) at week 4; 95 (34%) at week 16; 43 (28%) at 1-year] was insufficient to undertake any formal hypothesis testing and the trial was closed early. The groups were generally well balanced in terms of characteristics and percentage providing data, but more of those providing valid data had a previous conviction than those who did not provide data. Similar percentages from each arm provided data with those attending interviews completing all sections. Telephone interviews were acceptable to those willing to share an active telephone number. Rates for those who were non-contactable were similar between the groups at all three time points. Eighty-one of the 101 allocated to Gateway complied with the intervention. Reasons for non-compliance were reoffending and non-attendance at the LINX workshops. Qualitative evaluation: Across 3 time points, 69 in-depth interviews were conducted with: 28 young people, 25 Gateway staff, 13 police recruiters and 3 focus groups with navigators. The researchers were unable to pursue interviews with victims as there were few offences with a victim. Our findings showed that, following engagement with the Gateway programme, young people reported being better able to make decisions after engagement with the LINX workshops, while navigators played a significant role in enabling compliance and change among young people. The role of the navigator was akin to that of the mentor, providing practical support towards improved health including, for example, making and attending doctors' appointments with clients, as well as offering a listening role. Young people felt that, for them, the wider determinants (or 'areas') addressed with navigators, such as access to employment or improved health, were of greater importance than a reduction in reoffending. There was a polarity of needs among young people, which meant that all stakeholders valued the ability to tailor and adapt the programme to individual client's needs, also giving clients a sense of agency and control over their lives. The independence of the Gateway intervention team, from the police, was highly valued by young people. Factors related to communication were a concern for all, particular at the point of recruitment (by police) and between multiple delivery agencies. Discussion: The problems encountered throughout this trial and the researchers' endeavours to overcome these problems provide valuable insights for colleagues seeking to design similar interventions and/or conduct studies with vulnerable populations in the police setting. Co-production is essential for studies in the police setting. By working in close collaboration with HC , and their two project dedicated officers, the researchers were able to make pragmatic adjustments to the study design as issues arose. However, training an entire police force is fraught with difficulty even when supported by senior officers; competing interests precluded mandatory training for research purposes. The use of a two-stage consent process and a web-based eligibility and randomisation tool facilitate recruitment in the police setting, but frequent, regular need to use is required to maintain the study profile. Young people who have committed an offence are known to be a difficult group to engage with generally, let alone in research. The study identified and tested implementation of different approaches to overcome this problem. Switching to telephone interviews produced a positive response. Persistence and engagement paid off, but the study was unable to solve the problem of inactive mobile telephone numbers; an issue shared by the navigators and police. Independence of those delivering the intervention is important as perceived links with the police caused some disengagement. The collected data provide valuable information on attrition rates for health studies. Interestingly, allocation did not appear to make any difference to participation. The study's qualitative evaluation highlighted the unmet health needs for this group of 18- to 24-year-olds, and the need to address the wider determinants of reoffending through individualised assessment. The Gateway programme was, however, developed for those with higher needs, which meant that flexibility and adaptability to suit individual needs was essential. It further highlighted the invaluable role of mentors in rehabilitative programmes such as Gateway. The study has demonstrated that it is possible to recruit and randomise to a RCT in the police setting. The data that the study presents should be used to inform the planning of future trials, including anticipated attrition rates, and setting conservative targets for retention as well as recruitment rates. Internal pilots should be long enough to confirm recruitment and data collection rates are achievable over an adequate follow-up period. Given the challenges encountered, alternative study designs should be considered for the evaluation of interventions with a health-related outcome. These include: cluster RCTs where processes at individual cluster sites could be simplified; post hoc cohort studies which may address non-response and attrition bias; and regression discontinuity design (RDD), a quasi-experimental approach at lower risk of bias which has the potential to equate to a RCT. Conclusions: This ambitious RCT and qualitative study provides information about an out-of-court intervention aimed at improving life chances, health and well-being and recidivism in young adults. Challenges encountered in participation and retention in this setting and the ways in which these may be addressed are described and will be useful in planning future research. Study registration: This study is registered as ISRCTN11888938. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: 16/122/20) and is published in full in Public Health Research; Vol. 12, No. 7. See the NIHR Funding and Awards website for further award information. [ABSTRACT FROM AUTHOR]

Genetic toxicity testing assesses the potential of compounds to cause DNA damage. There are many genetic toxicology screening assays designed to assess the DNA damaging potential of chemicals in early drug development aiding the identification of promising drugs that have low-risk potential for causing genetic damage contributing to cancer risk in humans. Despite this, in vitro tests generate a high number of misleading positives, the consequences of which can lead to unnecessary animal testing and/or the abandonment of promising drug candidates. Understanding chemical Mode of Action (MoA) is vital to identifying the true genotoxic potential of substances and, therefore, the risk translation into the clinic. Here we demonstrate a simple, robust protocol for staining fixed, human-lymphoblast p53 proficient TK6 cells with antibodies against ɣH2AX, p53 and pH3S28 along with DRAQ5™ DNA staining that enables analysis of un-lysed cells via microscopy approaches such as imaging flow cytometry. Here, we used the Cytek® Amnis® ImageStream®X Mk II which provides a high-throughput acquisition platform with the sensitivity of flow cytometry and spatial morphological information associated with microscopy. Using the ImageStream manufacturer's software (IDEAS® 6.2), a masking strategy was developed to automatically detect and quantify micronucleus events (MN) and characterise biomarker populations. The gating strategy developed enables the generation of a template capable of automatically batch processing data files quantifying cell-cycle, MN, ɣH2AX, p53 and pH3 populations simultaneously. In this way, we demonstrate how a multiplex system enables DNA damage assessment alongside MN identification using un-lysed cells on the imaging flow cytometry platform. As a proof-of-concept, we use the tool chemicals carbendazim and methyl methanesulphonate (MMS) to demonstrate the assay's ability to correctly identify clastogenic or aneugenic MoAs using the biomarker profiles established. [ABSTRACT FROM AUTHOR]

Not discounting the important foetal or placental contribution, the endometrium is a key determinant of pregnancy outcomes. Given the inherently linked processes of menstruation, pregnancy and parturition with the endometrium, further understanding of menstruation will help to elucidate the maternal contribution to pregnancy. Endometrial health can be assessed via menstrual history and menstrual fluid, a cyclically shed, easily and non-invasively accessible biological sample that represents the distinct, heterogeneous composition of the endometrial environment. Menstrual fluid has been applied to the study of endometriosis, unexplained infertility and early pregnancy loss; however, it is yet to be examined regarding adverse pregnancy outcomes. These adverse outcomes, including preeclampsia, foetal growth restriction (FGR), spontaneous preterm birth and perinatal death (stillbirth and neonatal death), lay on a spectrum of severity and are often attributed to placental dysfunction. The source of this placental dysfunction is largely unknown and may be due to underlying endometrial abnormalities or endometrial interactions during placentation. We present existing evidence for the endometrial contribution to adverse pregnancy outcomes and propose that a more comprehensive understanding of menstruation can provide insight into the endometrial environment, offering great potential value as a diagnostic tool to assess pregnancy risk. As yet, this concept has hardly been explored. [ABSTRACT FROM AUTHOR]

Becker muscular dystrophy (BMD) is characterised by fiber loss and expansion of fibrotic and adipose tissue. Several cells interact locally in what is known as the degenerative niche. We analysed muscle biopsies of controls and BMD patients at early, moderate and advanced stages of progression using Hyperion imaging mass cytometry (IMC) by labelling single sections with 17 markers identifying different components of the muscle. We developed a software for analysing IMC images and studied changes in the muscle composition and spatial correlations between markers across disease progression. We found a strong correlation between collagen-I and the area of stroma, collagen-VI, adipose tissue, and M2-macrophages number. There was a negative correlation between the area of collagen-I and the number of satellite cells (SCs), fibres and blood vessels. The comparison between fibrotic and non-fibrotic areas allowed to study the disease process in detail. We found structural differences among non-fibrotic areas from control and patients, being these latter characterized by increase in CTGF and in M2-macrophages and decrease in fibers and blood vessels. IMC enables to study of changes in tissue structure along disease progression, spatio-temporal correlations and opening the door to better understand new potential pathogenic pathways in human samples. [ABSTRACT FROM AUTHOR]

The purpose of this document is to provide guidance for establishing and maintaining growth and development of flow cytometry shared resource laboratories. While the best practices offered in this manuscript are not intended to be universal or exhaustive, they do outline key goals that should be prioritized to achieve operational excellence and meet the needs of the scientific community. Additionally, this document provides information on available technologies and software relevant to shared resource laboratories. This manuscript builds on the work of Barsky et al. 2016 published in Cytometry Part A and incorporates recent advancements in cytometric technology. A flow cytometer is a specialized piece of technology that require special care and consideration in its housing and operations. As with any scientific equipment, a thorough evaluation of the location, space requirements, auxiliary resources, and support is crucial for successful operation. This comprehensive resource has been written by past and present members of the International Society for Advancement of Cytometry (ISAC) Shared Resource Laboratory (SRL) Emerging Leaders Program https://isac-net.org/general/custom.asp?page=SRL-Emerging-Leaders with extensive expertise in managing flow cytometry SRLs from around the world in different settings including academia and industry. It is intended to assist in establishing a new flow cytometry SRL, re‐purposing an existing space into such a facility, or adding a flow cytometer to an individual lab in academia or industry. This resource reviews the available cytometry technologies, the operational requirements, and best practices in SRL staffing and management. [ABSTRACT FROM AUTHOR]

Analysis of imaging mass cytometry (IMC) data and other low‐resolution multiplexed tissue imaging technologies is often confounded by poor single‐cell segmentation and suboptimal approaches for data visualization and exploration. This can lead to inaccurate identification of cell phenotypes, states, or spatial relationships compared to reference data from single‐cell suspension technologies. To this end we have developed the "OPTimized Imaging Mass cytometry AnaLysis (OPTIMAL)" framework to benchmark any approaches for cell segmentation, parameter transformation, batch effect correction, data visualization/clustering, and spatial neighborhood analysis. Using a panel of 27 metal‐tagged antibodies recognizing well‐characterized phenotypic and functional markers to stain the same Formalin‐Fixed Paraffin Embedded (FFPE) human tonsil sample tissue microarray over 12 temporally distinct batches we tested several cell segmentation models, a range of different arcsinh cofactor parameter transformation values, 5 different dimensionality reduction algorithms, and 2 clustering methods. Finally, we assessed the optimal approach for performing neighborhood analysis. We found that single‐cell segmentation was improved by the use of an Ilastik‐derived probability map but that issues with poor segmentation were only really evident after clustering and cell type/state identification and not always evident when using "classical" bivariate data display techniques. The optimal arcsinh cofactor for parameter transformation was 1 as it maximized the statistical separation between negative and positive signal distributions and a simple Z‐score normalization step after arcsinh transformation eliminated batch effects. Of the five different dimensionality reduction approaches tested, PacMap gave the best data structure with FLOWSOM clustering out‐performing phenograph in terms of cell type identification. We also found that neighborhood analysis was influenced by the method used for finding neighboring cells with a "disc" pixel expansion outperforming a "bounding box" approach combined with the need for filtering objects based on size and image‐edge location. Importantly, OPTIMAL can be used to assess and integrate with any existing approach to IMC data analysis and, as it creates.FCS files from the segmentation output and allows for single‐cell exploration to be conducted using a wide variety of accessible software and algorithms familiar to conventional flow cytometrists. [ABSTRACT FROM AUTHOR]

Introduction: We studied the impact of the use of three‐dimensional multidetector computed tomography (3D‐MDCT) and fluoroscopy fusion on percutaneous left atrial appendage occlusion (LAAO) procedures in relation to procedure time, contrast volume, fluoroscopy time, and total radiation. Methods: This was a single‐center, prospective, single‐blinded, randomized control trial. Patients meeting criteria for LAAO were randomized to undergo LAAO with the WATCHMAN FLXTM device with and without 3D‐MDCT‐fluoroscopy fusion guidance using a prespecified protocol using computed tomography angiography for WATCHMAN FLXTM sizing, moderate sedation, and intracardiac echocardiography for procedural guidance. Results: Overall, 59 participants were randomly assigned to the fusion (n = 33) or no fusion (n = 26) groups. The median (interquartile range) age was 79 (75–83) years, 24 (41%) were female, and 55 (93%) were Caucasian. The median CHA2DS2 VASc and HASBLED scores were 5 (4–6) and 3 (3–4), respectively. At the time of the study, 51 (53%) patients were on a direct acting oral anticoagulant. There were no significant differences between the fusion and no fusion groups in procedure time (52.4 ± 15.4 vs. 56.8 ± 19.5 min, p =.36), mean contrast volume used (33.8 ± 12.0 vs. 29.6 ± 11.5 mls, p =.19), mean fluoroscopy time (31.3 ± 9.9 vs. 28.9 ± 8.7 min, p =.32), mean radiation dose (1177 ± 969 vs. 1091 ± 692 mGy, p =.70), and radiation dose product curve (23.9 ± 20.5 vs. 35.0 ± 49.1 Gy cm2, p =.29). There was no periprosthetic leak in the two groups in the immediate 1‐month postprocedure follow‐up periods. Conclusions: There was no significant difference with and without 3D‐MDCT‐fluoroscopy fusion in procedure time, contrast volume use, radiation dose, and radiation dose product. [ABSTRACT FROM AUTHOR]

INTRODUCTION In response to COVID-19, the South African government banned the sale of tobacco products for 20 weeks. Before the ban, the illicit cigarette market was well-entrenched and smoking cessation services were not widely available. Several surveys conducted to ascertain cigarette smokers' responses to the ban reported substantial differences in the proportion of smokers who quit. This study provides a broadly nationally representative ex-post investigation into cigarette smokers' quitting behavior related to the sales ban. METHODS We used data from wave three of NIDS-CRAM (the National Income Dynamics Study-Coronavirus Rapid Mobile Survey) conducted in November-- December 2020. We first investigated the proportion of people who quit and who continued smoking during and after the sales ban. We subsequently linked the NIDS-CRAM survey to the fifth wave of NIDS (2017) to identify a subset of established smokers, and considered whether their quitting behavior differed from that of all smokers who smoked at the start of the sales ban. RESULTS The cross-sectional analysis showed that 7.8% of cigarette smokers quit during the sales ban, but that 55% of these quitters relapsed after it was lifted. Of the pre-ban smokers, 3.5% indicated that they did not smoke both during and after the sales ban, and 3.7% quit after the ban was lifted. The longitudinal analysis showed that 7% of people who were smoking in 2017, quit smoking cigarettes during the tobacco sales ban, but that >70% of quitters relapsed after it was lifted. Only 2% of pre-ban established smokers indicated that they did not smoke during or after the ban. CONCLUSIONS The sales ban did not have the intended objective of encouraging large-scale smoking cessation. This reflects policy failures to provide smokers with appropriate cessation support and to effectively control the illicit market both prior to and during the sales ban. [ABSTRACT FROM AUTHOR]

T cells play key protective but also pathogenic roles in COVID-19. We studied the expression of long non-coding RNAs (lncRNAs) in COVID-19 T-cell transcriptomes by integrating previously published single-cell RNA sequencing datasets. The long intergenic non-coding RNA MALAT1 was the most highly transcribed lncRNA in T cells, with Th1 cells demonstrating the lowest and CD8+ resident memory cells the highest MALAT1 expression, amongst CD4+ and CD8+ T-cells populations, respectively. We then identified gene signatures that covaried with MALAT1 in single T cells. A significantly higher number of transcripts correlated negatively with MALAT1 than those that correlated. Enriched functional annotations of the MALAT1- anti-correlating gene signature included processes associated with T-cell activation such as cell division, oxidative phosphorylation, and response to cytokine. The MALAT1 anti-correlating gene signature shared by both CD4+ and CD8+ T-cells marked dividing T cells in both the lung and blood of COVID-19 patients. Focussing on the tissue, we used an independent patient cohort of post-mortem COVID-19 lung samples and demonstrated that MALAT1 suppression was indeed a marker of MKI67+ proliferating CD8+ T cells. Our results reveal MALAT1 suppression and its associated gene signature are a hallmark of human proliferating T cells. T cells play important roles in the body's response to COVID-19. We found gene signatures anti-correlating to MALAT1 expression as a marker of proliferating CD4+ Th1 and CD8+ exhausted sub-populations. [ABSTRACT FROM AUTHOR]

Innate lymphoid cells (ILCs) play a key role in tissue-mediated immunity and can be controlled by coreceptor signaling. Here, we define a subset of ILCs that are Tbet+NK1.1- and are present within the tumor microenvironment (TME). We show programmed death-1 receptor (PD-1) expression on ILCs within TME is found in Tbet+NK1.1- ILCs. PD-1 significantly controlled the proliferation and function of Tbet+NK1.1- ILCs in multiple murine and human tumors. We found tumor-derived lactate enhanced PD-1 expression on Tbet+NK1.1- ILCs within the TME, which resulted in dampened the mammalian target of rapamycin (mTOR) signaling along with increased fatty acid uptake. In line with these metabolic changes, PD-1-deficient Tbet+NK1.1- ILCs expressed significantly increased IFNγ and granzyme B and K. Furthermore, PD-1-deficient Tbet+NK1.1- ILCs contributed toward diminished tumor growth in an experimental murine model of melanoma. These data demonstrate that PD-1 can regulate antitumor responses of Tbet+NK1.1- ILCs within the TME. [ABSTRACT FROM AUTHOR]

Background Patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF) are at increased stroke risk in comparison to those with non-valvular AF not affected by HCM. Objectives To investigate the role of left atrial appendage closure (LAAC) in patients with HCM and AF. Methods and results We identified patients with HCM and AF using the National Readmission Dataset. Patients were stratified based on LAAC status. The primary efficacy outcome was a composite of ischaemic and haemorrhagic stroke, TIA, and all-cause mortality. The primary safety outcome was a composite of major bleeding and pericardial complications. Patients were matched using inverse probability of treatment weighting. Cox-proportional hazard regression was applied to calculate the hazard ratio (HR) with a 95% confidence interval (CI) on matched cohorts. We identified 71 980 patients with HCM and AF. 1351 (1.9%) patients underwent LAAC. Two hundred and eighty-seven (21.2%) underwent transcatheter LAAC. LAAC was associated with a lower risk of the primary efficacy outcome (2.5% vs. 5.4%, HR: 0.38; 95% CI: 0.17–0.88; P = 0.024), the primary safety outcome (2.9% vs. 6.8%, HR: 0.39; 95% CI: 0.23–0.66, P = 0.001), and reduced major bleeding. The LAAC group trended towards a lower risk of ischaemic stroke and all-cause mortality. Conclusion Surgical and transcatheter LAAC was associated with a lower risk of haemorrhagic stroke and major bleeding. [ABSTRACT FROM AUTHOR]

Introduction Despite high levels of illicit trade in the tobacco market, the South African government banned the sale of tobacco products in March 2020 as part of its COVID-19 response. The ban lasted five months. We assess how the ban affected the cigarette market for a sample of smokers by comparing the price, consumption, and competitive landscapes before (March), during (May and June), and after (September) the ban. Methods We conducted three online surveys of cigarette smokers, asking about smoking behavior before, during, and after the ban. We use descriptive statistics and OLS regressions to estimate the impact of the ban on the South African cigarette market, focusing on the price of cigarettes. Results Most smokers continued smoking despite the sales ban. During the ban, prices increased by over 240%. Purchases shifted away from the normally dominant brands of the multinational tobacco companies to local/regional producers. The covariates of price changed substantially during the sales ban, the most pronounced being inter-provincial effects. After the ban, the market shifted back to its preban state, with an overall increase in price of 3.6%. Conclusions Cigarette sales continued despite the sales ban, further entrenching an already large illicit market. Had the government substantially increased the excise tax, rather than banned the sale of tobacco products, it would have achieved a similar public health outcome, received more revenue, and presumably not further entrenched the illicit market. Implications South Africa temporarily banned the sale of tobacco as part of its COVID-19 response. Despite the ban, the sale of cigarettes did not cease; rather, it caused major disruption to the cigarette market. The ban inadvertently benefited manufacturers who were previously disproportionately involved in illicit activities; these manufacturers increased their market share even after the ban was lifted. The ban may have further entrenched South Africa's already large illicit market. Our results show that there are unintended consequences associated with a temporary ban on the sale of cigarettes. [ABSTRACT FROM AUTHOR]

Background: Tobacco consumption is a contributing and modifiable risk factor for non-communicable diseases. In high-income countries, tobacco cessation attempts, and their success, are concentrated among the socio-economically advantaged, resulting in a skewed burden of disease. However, there is a paucity of evidence on the distribution of tobacco cessation in low- and middle-income countries. Objective: The objective of this study is to measure and decompose wealth- and education-related inequalities in tobacco cessation in eight Sub-Saharan African countries. Methodology: The study applies Erreygers' corrected concentration indices and decomposition methods to the most recent Global Adult Tobacco Surveys in Botswana, Cameroon, Ethiopia, Kenya, Nigeria, Senegal, Tanzania, and Uganda. Findings: We find that across countries, successful tobacco cessation, as well as tobacco cessation attempts, are concentrated among wealthier and better-educated individuals. Differences in socio-economic status, urban or rural residence, and not knowing or believing that tobacco consumption leads to serious illness contributes to these inequalities Conclusion: Governments in our sample of countries can do more to support socio-economically disadvantaged smokers in their efforts to quit smoking, including by making an effort to align each country's smoking cessation strategy with the guidelines outlined in the World Health Organization's Framework Convention on Tobacco Control. [ABSTRACT FROM AUTHOR]

Against the backdrop of a global pandemic, the Society for Reproductive Biology (SRB) 2021 meeting reunited the Australian and New Zealand reproductive research community for the first time since 2019 and was the first virtual SRB meeting. Despite the recent global research disruptions, the conference revealed significant advancements in reproductive research, the importance of which span human health, agriculture, and conservation. A core theme was novel technologies, including the use of medical microrobots for therapeutic and sperm delivery, diagnostic hyperspectral imaging, and hydrogel condoms with potential beyond contraception. The importance of challenging the contraceptive status quo was further highlighted with innovations in gene therapies, non-hormonal female contraceptives, epigenetic semen analysis, and in applying evolutionary theory to suppress pest population reproduction. How best to support pregnancies, particularly in the context of global trends of increasing maternal age, was also discussed, with several promising therapies for improved outcomes in assisted reproductive technology, pre-eclampsia, and pre-term birth prevention. The unique insights gained via non-model species was another key focus and presented research emphasised the importance of studying diverse systems to understand fundamental aspects of reproductive biology and evolution. Finally, the meeting highlighted how to effectively translate reproductive research into policy and industry practice. The Society for Reproductive Biology (SRB) is an Australian and New Zealand based organisation that supports basic and applied research across all aspects of reproductive biology. This review highlights the key themes from the annual SRB meeting, which was held virtually in 2021. Topics included novel technologies in reproduction, advances in contraception, non-model species, reproductive ageing and sustaining a pregnancy. [ABSTRACT FROM AUTHOR]

Lung transplantation is the optimal treatment for selected patients with end-stage chronic lung diseases. However, chronic lung allograft dysfunction remains the leading obstacle to improved long-term outcomes. Traditionally, lung allograft rejection has been considered primarily as a manifestation of cellular immune responses. However, in reality, an array of complex, interacting and multifactorial mechanisms contribute to its emergence. Alloimmune-dependent mechanisms, including T-cell-mediated rejection and antibodymediated rejection, as well as non-alloimmune injuries, have been implicated. Moreover, a role has emerged for autoimmune responses to lung self-antigens in the development of chronic graft injury. The aim of this review is to summarise the immune processes involved in the pathogenesis of chronic lung allograft dysfunction, with advanced insights into the role of innate immune pathways and crosstalk between innate and adaptive immunity, and to identify gaps in current knowledge. [ABSTRACT FROM AUTHOR]

Introduction: African countries have among the lowest excise taxes in the world. This paper provides new evidence on the association between cigarette prices and youth smoking in 16 African countries.Aims and Methods: We use Global Youth Tobacco Survey (GYTS) cross-country data from approximately 67 500 participants. The relationship between prices and youth smoking in Africa is estimated using probit models for smoking participation and generalized linear models for conditional cigarette demand. Each model is estimated using local-brand and foreign-brand cigarette prices.Results: Higher prices are associated with lower demand across African countries, for both smoking prevalence and the intensity of cigarette consumption by smokers. The estimated price elasticity of participation is -0.70 [95% CI: -1.28 to -0.12] for local-brand cigarettes and -0.71 [95% CI: -0.98 to -0.44] for foreign-brand cigarettes. The price elasticity of conditional cigarette demand is -0.44 [95% CI: -0.76 to -0.12] for local brands and -0.75 [95% CI: -0.96 to -0.53] for foreign brands. The total price elasticity of demand for youth in our sample is -1.14 for local brands and -1.46 for foreign brands.Conclusions: Higher cigarette prices significantly decrease the likelihood of smoking and decrease the intensity of cigarette consumption among African youths. Increases in the excise tax that increase the retail price of cigarettes will play an important role in reducing youth tobacco use on the continent. Governments are encouraged to increase excise taxes in order to improve public health.Implications: Evidence on the association between cigarette prices and youth smoking in African countries is limited. The Global Youth Tobacco Survey (GYTS) was first introduced in 1999. In 2012, the Centers for Disease Control and Prevention revised the GYTS questionnaire, which removed some questions and introduced new questions into the survey. To the best of our knowledge, there are no published estimates of the relationship between cigarette prices and demand that have used this more recent individual-level GYTS data for African countries. In conducting this analysis, we add to the limited literature on the association between cigarette prices and youth smoking in Africa. [ABSTRACT FROM AUTHOR]

Background: While there is recent data suggesting an advantage of computed tomography angiography (CTA) over transesophageal echocardiography (TEE) for preprocedural left atrial appendage closure (LAAC) planning, there is limited published experience for sizing strategies. Device sizing for LAAC may be challenging and noninvasive algorithms that improve this selection process are warranted. Objectives: We sought to evaluate the safety and the feasibility for the implementation of a novel CTA‐based sizing methodology for WATCHMAN™ FLX device in a series of patients undergoing LAAC using the TruPlan™ software package. Methods: A prospective analysis of 136 consecutive patients who underwent LAAC over a 12‐month period in a single, large academic hospital in the United States was conducted. CTA‐guided preprocedural planning and intracardiac echocardiography (ICE) was performed in all. Procedural success, adverse events, length of procedure, number of devices used, and length of stay were evaluated. Results: A total of 136 patients who underwent LAAC procedure with WATCHMAN™ FLX platform between October 1, 2020 until September 30, 2021 were included. The pre‐specified protocol using CTA and ICE was implemented in all patients (100%). Mean CHA2DS2VASc score was 4.4 ± 1.3 and the mean HAS‐BLED score was 3.9 ± 0.8. ICE‐guided 100% transseptal puncture success rate was 100% with 98.5% of overall procedural success rate. Preprocedural CTA sizing strategy accurately predicted the implanted size in 91.1% of patients. Ten patients (7.4%) required another sized device and 2 cases were aborted. At 45‐day follow‐up, only 1 patient (0.7%) had significant peri‐device leak (≥5 mm) on TEE. Conclusions: CTA‐based preprocedural sizing methodology for WATCHMAN™ FLX in LAAC was safe, feasible and associated with excellent procedural outcomes. Further studies are warranted to confirm if the features specific to TruPlan™ may reduce the number of deployment attempts, the number of devices utilized in the procedure, and the risk of complications. [ABSTRACT FROM AUTHOR]

Chronic lung allograft dysfunction (CLAD) remains the major barrier to long‐term survival after lung transplantation and improved insight into its underlying immunological mechanisms is critical to better understand the disease and to identify treatment targets. We systematically searched the electronic databases of PubMed and EMBASE for original research publications, published between January 2000 and April 2021, to comprehensively assess current evidence on effector immune cells in lung tissue and bronchoalveolar lavage fluid from lung transplant recipients with CLAD. Literature search revealed 1351 articles, 76 of which met the criteria for inclusion in our analysis. Our results illustrate significant complexity in both innate and adaptive immune cell responses in CLAD, along with presence of numerous immune cell products, including cytokines, chemokines and proteases associated with tissue remodelling. A clear link between neutrophils and eosinophils and CLAD incidence has been seen, in which eosinophils more specifically predisposed to restrictive allograft syndrome. The presence of cytotoxic and T‐helper cells in CLAD pathogenesis is well‐documented, although it is challenging to draw conclusions about their role in tissue processes from predominantly bronchoalveolar lavage data. In restrictive allograft syndrome, a more prominent humoral immune involvement with increased B cells, immunoglobulins and complement deposition is seen. Our evaluation of published studies over the last 20 years summarizes the complex multifactorial immunopathology of CLAD onset and progression. It highlights the phenotype of several key effector immune cells involved in CLAD pathogenesis, as well as the paucity of single cell resolution spatial studies in lung tissue from patients with CLAD. [ABSTRACT FROM AUTHOR]

Background: Papillary muscle rupture is a rare condition. Its clinical presentation, diagnosis and management can be very challenging for the clinician.Case Presentation: A 73-year-old woman with hypertension presented with chest pain, ST-segment changes, and elevated serum troponin levels. Coronary angiography was normal. Echocardiography revealed normal ventricular function, flail posterior mitral leaflet, and severe mitral regurgitation. She underwent emergent mitral valve replacement.Conclusion: The diagnostic and management strategies of this uncommon presentation are discussed. [ABSTRACT FROM AUTHOR]

SCAD is an entity that in recent years has had changes in the indication of the ideal type of treatment, since the percutaneous treatment of these lesions can be challenging and the results of long-term clinical treatment are encouraging [[1]]. Introduction Spontaneous coronary artery dissection (SCAD) is an entity that in recent years has had changes in the indication of the ideal type of treatment, since the percutaneous treatment of these lesions can be challenging and the results of long-term clinical treatment are encouraging [[1]]. Intravascular imaging by Optical Coherence Tomography (OCT) provides a very detailed assessment of the coronary including the demonstration of potential mechanisms of SCAD and can aggregate a lot of important information to its treatment. [Extracted from the article]

Background: Mitochondrial dysfunction within neurons, particularly those of the substantia nigra, has been well characterized in Parkinson's disease and is considered to be related to the pathogenesis of this disorder. Dysfunction within this important organelle has been suggested to impair neuronal communication and survival; however, the reliance of astrocytes on mitochondria and the impact of their dysfunction on this essential cell type are less well characterized. Objective: This study aimed to uncover whether astrocytes harbor oxidative phosphorylation (OXPHOS) deficiencies in Parkinson's disease and whether these deficiencies are more likely to occur in astrocytes closely associated with neurons or those more distant from them. Methods: Postmortem human brain sections from patients with Parkinson's disease were subjected to imaging mass cytometry for individual astrocyte analysis of key OXPHOS proteins across all five complexes. Results: We show the variability in the astrocytic expression of mitochondrial proteins between individuals. In addition, we found that there is evidence of deficiencies in respiratory chain subunit expression within these important glia and changes, particularly in mitochondrial mass, associated with Parkinson's disease and that are not simply a consequence of advancing age. Conclusion: Our data show that astrocytes, like neurons, are susceptible to mitochondrial defects and that these could have an impact on their reactivity and ability to support neurons in Parkinson's disease. [ABSTRACT FROM AUTHOR]

The in vitro micronucleus assay is a globally significant method for DNA damage quantification used for regulatory compound safety testing in addition to inter-individual monitoring of environmental, lifestyle and occupational factors. However, it relies on time-consuming and user-subjective manual scoring. Here we show that imaging flow cytometry and deep learning image classification represents a capable platform for automated, inter-laboratory operation. Images were captured for the cytokinesis-block micronucleus (CBMN) assay across three laboratories using methyl methanesulphonate (1.25–5.0 μg/mL) and/or carbendazim (0.8–1.6 μg/mL) exposures to TK6 cells. Human-scored image sets were assembled and used to train and test the classification abilities of the "DeepFlow" neural network in both intra- and inter-laboratory contexts. Harnessing image diversity across laboratories yielded a network able to score unseen data from an entirely new laboratory without any user configuration. Image classification accuracies of 98%, 95%, 82% and 85% were achieved for 'mononucleates', 'binucleates', 'mononucleates with MN' and 'binucleates with MN', respectively. Successful classifications of 'trinucleates' (90%) and 'tetranucleates' (88%) in addition to 'other or unscorable' phenotypes (96%) were also achieved. Attempts to classify extremely rare, tri- and tetranucleated cells with micronuclei into their own categories were less successful (≤ 57%). Benchmark dose analyses of human or automatically scored micronucleus frequency data yielded quantitation of the same equipotent concentration regardless of scoring method. We conclude that this automated approach offers significant potential to broaden the practical utility of the CBMN method across industry, research and clinical domains. We share our strategy using openly-accessible frameworks. [ABSTRACT FROM AUTHOR]

Study Question: Does natural variation exist in the endometrial stem/progenitor cell and protein composition of menstrual fluid across menstrual cycles in women?Summary Answer: Limited variation exists in the percentage of some endometrial stem/progenitor cell types and abundance of selected proteins in menstrual fluid within and between a cohort of women.What Is Known Already: Menstrual fluid is a readily available biofluid that can represent the endometrial environment, containing endometrial stem/progenitor cells and protein factors. It is unknown whether there is natural variation in the cellular and protein content across menstrual cycles of individual women, which has significant implications for the use of menstrual fluid in research and clinical applications.Study Design, Size, Duration: Menstrual fluid was collected from 11 non-pregnant females with regular menstrual cycles. Participants had not used hormonal medications in the previous 3 months. Participants collected menstrual fluid samples from up to five cycles using a silicone menstrual cup worn on Day 2 of menstrual bleeding.Participants/materials, Setting, Methods: Menstrual fluid samples were centrifuged to separate soluble proteins and cells. Cells were depleted of red blood cells and CD45+ leucocytes. Menstrual fluid-derived endometrial stem/progenitor cells were characterized using multicolour flow cytometry including markers for endometrial stem/progenitor cells N-cadherin (NCAD) and stage-specific embryonic antigen-1 (SSEA-1) (for endometrial epithelial progenitor cells; eEPC), and sushi domain containing-2 (SUSD2) (for endometrial mesenchymal stem cells; eMSC). The clonogenicity of menstrual fluid-derived endometrial cells was assessed using colony forming unit assays. Menstrual fluid supernatant was analyzed using a custom magnetic Luminex assay.Main Results and the Role Of Chance: Endometrial stem/progenitor cells are shed in menstrual fluid and demonstrate clonogenic properties. The intraparticipant agreement for SUSD2+ menstrual fluid-derived eMSC (MF-eMSC), SSEA-1+ and NCAD+SSEA-1+ MF-eEPC, and stromal clonogenicity were moderate-good (intraclass correlation; ICC: 0.75, 0.56, 0.54 and 0.52, respectively), indicating limited variability across menstrual cycles. Endometrial inflammatory and repair proteins were detectable in menstrual fluid supernatant, with five of eight (63%) factors demonstrating moderate intraparticipant agreement (secretory leukocyte protein inhibitor (SLPI), lipocalin-2 (NGAL), lactoferrin, follistatin-like 1 (FSTL1), human epididymis protein-4 (HE4); ICC ranges: 0.57-0.69). Interparticipant variation was limited for healthy participants, with the exception of key outliers of which some had self-reported menstrual pathologies.Large Scale Data: N/A. There are no OMICS or other data sets relevant to this study.Limitations, Reasons For Caution: The main limitations to this research relate to the difficulty of obtaining menstrual fluid samples across multiple menstrual cycles in a consistent manner. Several participants could only donate across <3 cycles and the duration of wearing the menstrual cup varied between 4 and 6 h within and between women. Due to the limited sample size used in this study, wider studies involving multiple consecutive menstrual cycles and a larger cohort of women will be required to fully determine the normal range of endometrial stem/progenitor cell and supernatant protein content of menstrual fluid. Possibility for selection bias and true representation of the population of women should also be considered.Wider Implications Of the Findings: Menstrual fluid is a reliable source of endometrial stem/progenitor cells and related endometrial proteins with diagnostic potential. The present study indicates that a single menstrual sample may be sufficient in characterizing a variety of cellular and protein parameters across women's menstrual cycles. The results also demonstrate the potential of menstrual fluid for identifying endometrial and menstrual abnormalities in both research and clinical settings as a non-invasive method for assessing endometrial health.Study Funding/competing Interest(s): This study was supported by grants from the Australian National Health and Medical Research Council to C.E.G. (Senior Research Fellowship 1024298 and Investigator Fellowship 1173882) and to J.E. (project grant 1047756), the Monash IVF Research Foundation to C.E.G. and the Victorian Government's Operational Infrastructure Support Program. K.A.W., M.L.D.-T., S.G.S. and J.E. declare no conflicts of interest. C.E.G. reports grants from NHMRC, during the conduct of the study; grants from EndoFound USA, grants from Ferring Research Innovation, grants from United States Department of Defence, grants from Clue-Utopia Research Foundation, outside the submitted work. CEF reports grants from EndoFound USA, grants from Clue-Utopia Research Foundation, outside the submitted work. [ABSTRACT FROM AUTHOR]

Amid the coronavirus disease 2019 (COVID-19) pandemic, there is an unprecedented increase in public avoidance of hospitals predominantly driven by fear of contracting the virus. Recent publications highlight a re-emergence of rare post–myocardial infarction complications. While mechanical complications are infrequent in the era of primary percutaneous coronary intervention, they are associated with high mortality rates. The concurrent occurrence of mechanical complications such as left ventricular aneurysm and ventricular septal rupture is an extremely rare entity. We hereby delineate a unique case of a 53-year-old Caucasian male who underwent successful concomitant closure of a ventricular septal rupture, left ventricular aneurysmectomy, and 3-vessel coronary artery bypass grafting. Due to a delayed initial presentation owing to the patient's fear of contracting COVID-19, the surgery was carried out 3 months after the myocardial infarction. His postoperative evaluation confirmed normal contractility of the left ventricle and complete closure of the ventricular septal rupture. Six months postoperatively, the patient continues to do well. We also present a literature review of the mechanical complications following delayed presentation of myocardial infarction amid the COVID-19 pandemic. This article illustrates that clinicians should remain cognizant of these extremely rare but potentially lethal collateral effects during the ongoing global public-health challenge. Furthermore, it highlights a significant concern regarding the delay in first medical contact due to the reluctance of patients to visit the hospital during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Development of a branching tree in the embryonic lung is crucial for the formation of a fully mature functional lung at birth. Sox9+ cells present at the tip of the primary embryonic lung endoderm are multipotent cells responsible for branch formation and elongation. We performed a genetic screen in murine primary cells and identified aurora kinase b (Aurkb) as an essential regulator of Sox9+ cells ex vivo. In vivo conditional knockout studies confirmed that Aurkb was required for lung development but was not necessary for postnatal growth and the repair of the adult lung after injury. Deletion of Aurkb in embryonic Sox9+ cells led to the formation of a stunted lung that retained the expression of Sox2 in the proximal airways, as well as Sox9 in the distal tips. Although we found no change in cell polarity, we showed that loss of Aurkb or chemical inhibition of Aurkb caused Sox9+ cells to arrest at G2/M, likely responsible for the lack of branch bifurcation. This work demonstrates the power of genetic screens in identifying novel regulators of Sox9+ progenitor cells and lung branching morphogenesis. [ABSTRACT FROM AUTHOR]

Background and Aims: Endoscopic eradication therapy (EET) is the first line approach for treating Barrett's oesophagus (BE) related neoplasia globally. The British Society of Gastroenterology (BSG) recommend EET with combined endoscopic resection (ER) for visible dysplasia followed by endoscopic ablation in patients with both low and high grade dysplasia (LGD and HGD). The aim of this study is to perform a cost-effectiveness analysis for EET for treatment of all grades of dysplasia in BE patients.Methods: A Markov cohort model with a lifetime time horizon was used to undertake a cost-effectiveness analysis. A hypothetical cohort of UK patients diagnosed with BE entered the model. Patients in the treatment arm with LGD and HGD received EET and patients with non-dysplastic BE (NDBE) received endoscopic surveillance only. In the comparator arm, patients with LGD, HGD and NDBE received endoscopic surveillance only. A UK National Health Service (NHS) perspective was adopted and the incremental cost-effectiveness ratio (ICER) was calculated. Sensitivity analysis was conducted on key input parameters.Results: EET for patients with LGD and HGD arising in BE is cost-effective compared to endoscopic surveillance alone (lifetime ICER £3006 per quality adjusted life year [QALY] gained). The results show that, as the time horizon increases, the treatment becomes more cost-effective. The 5 year financial impact to the UK NHS of introducing EET is £7.1m.Conclusions: EET for patients with low and high grade BE dysplasia, following updated guidelines from the BSG, has been shown to be cost-effective for patients with BE in the UK. [ABSTRACT FROM AUTHOR]